미세수술적 난관복원술 후 임신에 실패한 환자에서의 체외수정시술 결과

김석현,홍준석,구승엽,서창석,최영민,김정구,문신용,이진용,Kim, Seok-Hyun,Hong, Joon-Seok,Ku, Seung-Yup,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong 대한생식의학회 2001 Clinical and Experimental Reproductive Medicine Vol.28 No.4

Objective: To evaluate the clinical outcomes and influencing factors of in vitro fertilization and embryo transfer (IVF-ET) in patients with failed pregnancy after microsurgical reversal of tubal sterilization. Materials and Methods : From January, 1997 to December, 2000, IVF-ET was performed in two groups; the study TR (tubal reanastomosis) group consisted of 147 cycles in 66 patients with failed microsurgical reversal of tubal sterilization, and the control group of 115 cycles in 67 patients with bilateral tubal occlusion (BTO). The two groups were evaluated and compared for clinical characteristics, clinical pregnancy rates, and factors influencing the outcomes of IVF-ET. Results: Compared with the control BTO group, age and the previous parity were significantly higher ($36.3{\pm}2.7$ vs. $33.6{\pm}2.0$ years, p<0.05; $1.6{\pm}0.7$ vs. $0.2{\pm}0.4$, p<0.05), and the clinical pregnancy rate per cycle was significantly lower (23.8% (35/147) vs. 29.3% (34/115), p<0.05) in the TR group. Difference in the clinical pregnancy rates was age-related, since there was no significant difference between the two groups, except for the previous parity ($1.6{\pm}0.7$ vs. $0.1{\pm}0.3$, p<0.05), when the patients aged 37 years or older were excluded. No difference was found in terms of the following: the proportion of controlled ovarian hyperstimulation (COH) cycles with GnRH agonist ultrashort protocol, the duration of COH, the dosage of gonadotropins used, and the numbers of oocytes retrieved and of embryos transferred, irrespective of age correction. Conclusions: The outcomes of IVF-ET following the failed microsurgical reversal of tubal sterilization depend upon patient age. The previous fertility of patients does not seem to be a factor of better IVF-ET prognosis.

기초 혈중 Follicle Stimulating Hormone 농도가 높은 체외수정시술 환자의 과배란유도시 Gonadotropin-Releasing Hormone Agonist의 단기투여법과 장기투여법의 비교

김석현,송은섭,송용상,이경희,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Song, Eun-Seop,Song, Yong-Sang,Lee, Kyung-Hee,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong,Chang, Yoon-Seok 대한생식의학회 1991 Clinical and Experimental Reproductive Medicine Vol.18 No.2

Recently the application of gonadotropin-releasing hormone (GnRH) agonist to superovulation in previous poor responders has resulted in the improved outcomes after in vitro fertilization (IVF) outcome. However, poor responders with poor estradiol $(E_2)$ rise or single dominant follicle are a particularly challenging group. Recent reports have also shown that patients with higher basal serum follicle stimulating hormone (FSH) level, result in poorer ovarian response and lower pregnancy rate. Analysis of the differences of superovulation outcomes according to the different protocols of GnRH agonist, long (L, n = 18) and short (S, n = 16) protocols, in patients with high basal FSH levels (>20mIU/ml) were undertaken at Seoul National University Hospital from June to October 1990. The administration of GnRH agonist was begun on day 21 of the cycle in long protocol, and on day 2 in short protocol. Ages of patients and husbands, basal FSH and luteinizing hormone (LH) levels and FSH/LH ratio did not differ significantly. Types and causes of infertility were evenly distributed. Whereas the duration of stimulation and the amounts of gonadotropins administered were significantly reduced in short protocol, the numbers of oocytes retrieved and cleaved, the cleavage rate and the number of embryos transferred were higher in long protocol without statistical signifieance. The pregnancy rate per ET was 16.7% (2/12) in short protocol, and 17.6% (3/17) in long protocol. These data suggest that both protocols result in the similar superovulation outcomes in patients with higher basal serum FSH levels.

체외수정시술시 배아의 보조부화술을 이용한 임신율 향상에 관한 연구

김석현,김광례,채희동,이재훈,김희선,류범용,오선경,서창석,최영민,김정구,문신용,이진용,Kim, Seok-Hyun,Kim, Kwang-Rye,Chae, Hee-Dong,Lee, Jae-Hoon,Kim, Hee-Sun,Ryu, Buom-Yong,Oh, Sun-Kyung,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung-Gu,Moon, S 대한생식의학회 1997 Clinical and Experimental Reproductive Medicine Vol.24 No.1

In spite of much progress in vitro fertilization and embryo transfer (IVF-ET) program, the pregnancy rate remains at 20-30%, and the endometrial implantation rate per embryo transferred at 10-15%. As a result, about 90% of embryos may fail to implant to the endometrium, and many attempts such as optimization of follicular development, improvement of in vitro culture system including coculture, and micromanipulation of zona pellucida have been made to improve embryonic implantation after IVF-ET. Recently, several procedures of assisted hatching (AH) using micromanipulation have been introduced, and pregnancies and births have been obtained after AH. To develop and establish AH as an effective procedure to improve embryonic implantation, AH with partial zona dissection (PZD) was performed in 116 cycles of 89 infertile couples who had previous repeated failures of standard IVF-ET more than two times (Group I: 71 cycles in 54 patients), or who had implantation failure of embryos with good quality (Group II: 15 cycles in 13), or who had undergone AH without specific indication (Group III: 30 cycles in 22) from January, 1995 to Februry, 1996, and the outcomes of AH were analyzed according to pregnancy rate. The number of oocytes retrieved after controlled ovarian hyperstimulation (COH) was $9.9{\pm}7.1$ in Group I, $11.5{\pm}4.5$ in Group II, and $7.9{\pm}6.4$ in Group III. The number of embryos transferred after AH was $4.7{\pm}1.8$ in Group I, $5.3{\pm}1.3$ in Group II, and $3.5{\pm}2.4$ in Group III. The mean cumulative embryo score (CES) was $56.8{\pm}30.0$ in Group I, $76.1{\pm}35.9$ in Group II, and $38.5{\pm}29.9$ in Group III. The overall clinical pregnancy rate per cycle and per patient was 12.7% (9/71) and 16.7% (9/54) in Group I, 33.3% (5/15) and 38.5% (5/13) in Group II, and 6.7% (2/30) and 9.1% (2/22) in Group III, respectively. There were significant differences in the numbers of oocytes retrieved and embryos transferred, CES, and the clinical pregnancy rate per cycle among three groups. There was a significant inverse correlation between basal serum FSH level and CES, and no pregnancy occurred in patients with CES less than 20. In conclusion, AH of human embryos with PZD prior to ET has improved the implantation and pregnancy rates in IVF-ET patients with the past history of repeated failures, especially in spite of transfer of embryos with good quality, and AH will provide a range of novel techniques which may contribute much to effective management of infertile couples.

체외수정시술 후 임신된 환자에서 혈중 ${\beta}-hCG$ 측정에 의한 임신 결과 예측에 관한 연구

김석현,서창석,최두석,최영민,신창재,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Suh, Chang-Suk,Choi, Doo-Seok,Choi, Young-Min,Shin, Chang-Jae,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong,Chang, Yoon-Seok 대한생식의학회 1992 Clinical and Experimental Reproductive Medicine Vol.19 No.1

Serum level of ${\beta}$ subunit of human chorionic gonadotropin (${\beta}-hCG$) was studied to evaluate its predictability of pregnancy outcome in 98 in vitro fertilization and embryo transfer(IVF-ET) patients using gonadotropin-releasing hormone(GnRH) agonist. Serial serum ${\beta}-hCG$ levels were established for 42 singleton pregnancies, 20 normal multiple pregnancies, 18 preclinical abortions, 14 clinical abortions and 4 ectopic pregnancies. In comparison to normal singleton pregnancies, multiple pregnancies showed significantly higher ${\beta}-hCG$ levels on the post-ET day 10 to 13 and day 24 to 25. Clinical abortions did not show significantly lower ${\beta}-hCG$ levels in early pregnancy except the post-ET day 16-17, but showed significantly lower ${\beta}-hCG$ levels from the post-ET day 22, compared with singleton pregnancies. Preclinical abortions showed significantly lower ${\beta}-hCG$ levels than those of singleton pregnancies. Ectopic pregnancies showed lower ${\beta}-hCG$ levels than those of singleton pregnancies without statistical significance. In conclusion, determination of serum ${\beta}-hCG$ level in early pregnancy is a useful tool for the prediction of preclinical abortions and multiple pregnancies and serial measurement of serum ${\beta}-hCG$ levels will be helpful in predicting clinical abortion.

미세수술적 난관복원술을 시행받은 36세 이상 환자에서의 임신율에 관한 연구

김석현,이규창,최수희,최영민,신창재,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Lee, Gyu-Chang,Choi, Soo-Hee,Choi, Young-Min,Shin, Chang-Jae,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Young,Chang, Yoon-Seok 대한생식의학회 1998 Clinical and Experimental Reproductive Medicine Vol.25 No.3

Objective: To determine the reproductive outcomes of women undergoing microsurgical reversal of tubal sterilization at age 36 years or older. Materials and Methods: A series of 133 patients who received microsurgical reversal of the previously sterilized fallopian tubes at Seoul National University Hospital from July, 1980 to January, 1992 was reviewed and evaluated for clinical characteristics, pregnancy rates, and factors influencing the outcome of tubal reversal. Results: Of 133 patients, 78 (58.6%) had been sterilized by laparoscopic cautery. Loss of children was a leading cause for tubal reversal. The mean interval from tubal sterilization to tubal reversal was 65.0 months. The overall pregnancy rate was 52.6% (70/133), and the mean interval was 9.4 months from tubal reversal to pregnancy. Excluding 7 patients who were lost to follow-up, 76 pregnancies were confirmed in 63 patients with the delivery rate per patient of 66.7% (42/63). There were no significant differences in age, duration of tubal sterilization, postoperative tubal length between pregnant and non-pregnant groups. Conclusions: Microsurgical reversal of tubal sterilization could be a justifiable method in women 36 years age or older.

생식세포 난관내이식시 잉여난자의 체외수정 결과에 따른 임신 예측도

김석현,전종관,신창재,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Jun, Jong-Kwan,Shin, Chang-Jae,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong,Chang, Yoon-Seok 대한생식의학회 1992 Clinical and Experimental Reproductive Medicine Vol.19 No.1

By means of the results of In vitro fertilization(IVF) of supernumerary oocytes, the possibility of predicting a pregnancy outcome following gamete intrafallopian transfer(GIFT) and the prognostic implications for future pregnancy were evaluated in 46 GIFT cycles excluding simultaneous program of GIFT and IVF from February, 1989 to July, 1991. IVF of supernumerary oocytes were identified in 21 cycles, but not in remaining 25 cycles. There was no significant difference in age, duration and etiologic factors of infertility, and serum levels of FSH, LH and $E_2$ on MCD #3 and $E_2$ on the day of hCG injection between fertilized(N=21) and unfertilized group(N=25). The number of oocytes retrieved was similar in both groups. The number of supernumerary oocytes available for IVF after transfer was $5.43{pm}2.95$ ranging from 2 to 12. The prenancy rate in fertilized group, 33.3%(7/21), was higher without statistical significance, compared with 8.0%(2/25) in unfertilized group. Using IVF of supernumerary oocytes as a test of pregnancy following GIFT, sensitivity was 77.8 %; specificity, 61.2%; positive predictive value(PPV), 33.3%; negative predictive value(NPV), 92%. The fertilization rate of supernumerary oocytes in pregnant group, $86.4{\pm}22.8%$ was significantly higher compared with $56.1{\pm}20.2%$ in nonpregnant group. In cases with fertilization rate ${\geq}80%$, pregnancy was expected with PPV of 85.7%. In conclusion, IVF of supernumerary oocytes in GIFT program can be a profitable method as a prognostic indicator of pregnancy following GIFT. More aggressive diagnostic and therapeutic measures should be performed in cases with failure in IVF of supernumerary oocytes.

착상 전 유전진단 기술 개발의 동물실험 모델로서 할구 생검된 생쥐 배아에서 동결보존 융해 후 배아 발생 양상과 공배양 효과에 관한 연구

김석현,김희선,류범용,최성미,방명걸,오선경,지병철,서창석,최영민,김정구,문신용,이진용,채희동,김정훈,Kim, Seok-Hyun,Kim, Hee-Sun,Ryu, Buom-Yong,Choi, Sung-Mi,Pang, Myung-Geol,Oh, Sun-Kyung,Jee, Byung-Chul,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.1

Objective: The effects of cryopreservation with or without coculture on the in vitro development of blastomere-biopsied 8-cell mouse embryos were investigated. This experimental study was originally designed for the setup of a preclinical mouse model for the preimplantation genetic diagnosis (PGD) in human. Methods: Eight-cell embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BL(표현불가)/CBA(표현불가)). Using micromanipulation, one to four blastomeres were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acid Tyrode's solution (ATS). A slow-freezing and rapid-thawing protocol with 1.5M dimethyl sulfoxide (DMSO) and 0.1M sucrose as cryoprotectant was used for the cryopreservation of blastomere- biopsied 8-cell mouse embryos. After thawing, embryos were cultured for 110 hours in Ham's F-10 supplemented with 0.4% bovine serum albumin (BSA). In the coculture group, embryos were cultured for 110 hours on the monolayer of Vero cells in the same medium. The blastocyst formation was recorded, and the embryos developed beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. Results: The survival rate of embryos after cryopreservation was significantly lower in the blastomere-biopsied (7/8, 6/8, 5/8, and 4/8 embryos) groups than in the non-biopsied, zona intact (ZI) group. Without the coculture, the blastocyst formation rate of embryos after cryopreservation was not significantly different among ZI, the zona drilling only (ZD), and the balstomere-biopsied groups, but it was significantly lower than in the non-cryopreserved control group. The mean number of cells in embryos beyond blastocyst stage was significantly higher in the control group ($50.2{\pm}14.0$) than in 6/8 ($26.5{\pm}6.2$), 5/8 ($25.0{\pm}5.5$), and 4/8 ($17.8{\pm}7.8$) groups. With the coculture using Vero cells, the blastocyst formation rate of embryos after cryopreservation was significantly lower in 5/8 and 4/8 groups, compared with the control, 7/8, and 6/8 groups. The mean number of cells in embryos beyond blastocyst stage was also significantly lower in 4/8 group ($25.9{\pm}10.2$), compared with the control ($50.2{\pm}14.0$), 7/8 ($56.0{\pm}22.2$), and 6/8 ($55.3{\pm}25.5$) groups. Conclusion: After cryopreservation, blastomere-biopsied mouse embryos have a significantly impaired developmental competence in vitro, but this detrimental effect might be prevented by the coculture with Vero cells in 8-cell mouse embryos biopsied one or two blastomeres. Biopsy of mouse embryos after ZD with ATS is a safe and highly efficient preclinical model for PGD of human embryos.

한국인 남성을 대상으로 한 햄스터 난자 침투 분석법의 정상 가임역 설정

김석현,방명걸,신창재,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Pang, Myung-Geol,Shin, Chang-Jae,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong,Chang, Yoon-Seok 대한생식의학회 1991 Clinical and Experimental Reproductive Medicine Vol.18 No.1

To establish the normal fertile range in the results of the sperm zona-free hamster ova penetration assay (SPA) in Korean male, SPA using the low temperature ($4^{\circ}C$) capacitation in TEST-yolk buffer (TYB) was performed in 67 fertile and 26 infertile men. Sperm parameters in routine semen analysis were also checked and compared with the results of SPA. Sperm concentration, motility and motility index (MI) were significantly higher in fertile group compared with infertile group: $96.0{\pm}46.6$ vs $43.6{\pm}31.9{\times}10^6/ml$, $65.5{\pm}14.8%$ vs $45.8{\pm}23.6%$ and $46.31{\pm}13.29$ vs 27.40{\pm}17.98$, respectively. In fertile group, the hamster ova penetration rate (PR) was $98.5{\pm}5.0%$ (80%-100%), and the penetration index (mean penetrations per ovum, PI) was $9.59{\pm}6.35$(3.1-29.0). All the fertile men showed PI>3.0. In infertile group, PR was $24.6{\pm}24.8%$ (0%-70%), and PI was $0.40{\pm}0.42$ (0-1.3). Both PR and PI were significantly lower in infertile group. There was a significant correlation beween PI and sperm motility or MI, respectively, in fertile group whereas there was no correlation in infertile group. These data suggest that SPA using the low temperature capacitation in TYB can be a valuable diagnostic tool for the assessment of male fertility in vitro and provide an important supplement to the traditional tests of sperm quality.

골반결핵 기왕력이 있는 불임환자의 체외수정시술에 관한 연구

김석현,장윤석,Kim, Seok-Hyun,Chang, Yoon-Seok 대한생식의학회 1989 Clinical and Experimental Reproductive Medicine Vol.16 No.1

It has been suggested that the prognosis for fertility of the infertile patients with healed pelvic tuberculosis is very poor. Total 60 patients(77 cycles) with previous history of pelvic tuberculosis who underwent IVF-ET from January 1988 to March 1989 at SNUH were classified into three groups according to the principal histopathological lesions : tuberculous endometritis group(N=20, 28 cycles), tuberculous salpingitis group(N=32, 37 cycles) and pelvic peritoneal tuberculosis group(N=8, 12 cycles). To evaluate the effects of previous pelvic tuberculous lesions on ovarian follicular growth and development in controlled ovarian hyperstimulation for IVF-ET and its final outcome, serum E2 levels on the day of hCG administration(Day 0) and the day after hCG administration(Day +1), the number of ovarian follicles with mean diamete ${\geqq}$ 12 mm on Day 0, the number of oocytes retrieved by transvaginal aspiration, and pregnancy rate per cycle were measured and compared with control group(N=123, 161 cycles). There were no significant differences in cancellation rate during controlled ovarian hyperstimulation, total dosage of FSH and hMG administrated, menstrual cycle date(MCD) of hCG injection, serum E2 levels, the number of ovarian follicles with mean diameter ${\geqq}$ 15 mm, and the number of oocytes retrieved between pelvic tuberculosis group and control group. But in pelvic tuberculosis group, the number of ovarian follicles with mean diameter 12-14 mm, total number of ovarian follicles(${\geqq}$ 12 mm), and pregnancy rate per cycle were significantly decreased. These data suggest that previous pelvic tuberculous lesions have no significant adverse effects on the ovarian response to gonadotropin stimulation. IVF-ET proved to be an useful treatment modality for infertile patients with previous history of pelvic tuberculosis in spite of its relatively lowered pregnancy rate.

Fuzzy C-Means와 확률 C-Means를 결합한 정밀 영상측정 시스템 개발

김석현(Seok-Hyun Kim) 한국산업정보학회 1999 한국산업정보학회 학술대회논문집 Vol.1999 No.12